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The Journal of Neuroscience, August 18, 2004, 24(33):7387-7399; doi:10.1523/JNEUROSCI.0322-04.2004

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Cellular/Molecular
Contactin Associates with Sodium Channel Na_v1.3 in Native Tissues and Increases Channel Density at the Cell Surface

Bhaval S. Shah,^1,2,3 * Anthony M. Rush,^1,2,3 * Shujun Liu,^1,2,3 Lynda Tyrrell,^1,2,3 Joel A. Black,^1,2,3 Sulayman D. Dib-Hajj,^1,2,3 and Stephen G. Waxman^1,2,3

¹Department of Neurology and ²The Center for Neuroscience and Regeneration Research, Yale University School of Medicine, New Haven, Connecticut 06510, and ³Rehabilitation Research Center, Veterans Affairs Connecticut Healthcare Center, West Haven, Connecticut 06516

The upregulation of voltage-gated sodium channel Na_v1.3 has been linked to hyperexcitability of axotomized dorsal root ganglion (DRG) neurons, which underlies neuropathic pain. However, factors that regulate delivery of Na_v1.3 to the cell surface are not known. Contactin/F3, a cell adhesion molecule, has been shown to interact with and enhance surface expression of sodium channels Na_v1.2 and Na_v1.9. In this study we show that contactin coimmunoprecipitates with Na_v1.3 from postnatal day 0 rat brain where this channel is abundant, and from human embryonic kidney (HEK) 293 cells stably transfected with Na_v1.3 (HEK-Na_v1.3). Purified GST fusion proteins of the N and C termini of Na_v1.3 pull down contactin from lysates of transfected HEK 293 cells. Transfection of HEK-Na_v1.3 cells with contactin increases the amplitude of the current threefold without changing the biophysical properties of the channel. Enzymatic removal of contactin from the cell surface of cotransfected cells does not reduce the elevated levels of the Na_v1.3 current. Finally, we show that, similar to Na_v1.3, contactin is upregulated in axotomized DRG neurons and accumulates within the neuroma of transected sciatic nerve. We propose that the upregulation of contactin and its colocalization with Na_v1.3 in axotomized DRG neurons may contribute to the hyper-excitablity of the injured neurons.

Key words: axotomy; sensory neurons; cell adhesion molecule; neuroma; tetrodotoxin sensitive; GPI-anchor

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Received June 13, 2003; revised July 13, 2004; accepted July 13, 2004.

This article has been cited by other articles:

				Y. Kovalsky, R. Amir, and M. Devor Simulation in Sensory Neurons Reveals a Key Role for Delayed Na+ Current in Subthreshold Oscillations and Ectopic Discharge: Implications for Neuropathic Pain J Neurophysiol, September 1, 2009; 102(3): 1430 - 1442. [Abstract] [Full Text] [PDF]

				A. M. Rush, T. R. Cummins, and S. G. Waxman Multiple sodium channels and their roles in electrogenesis within dorsal root ganglion neurons J. Physiol., February 15, 2007; 579(1): 1 - 14. [Abstract] [Full Text] [PDF]

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